The use of adolescent nonhuman primates to model human alcohol intake - Neurobiological, genetic, and psychological variables
The use of adolescent nonhuman primates to model human alcohol intake - Neurobiological, genetic, and psychological variables
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DOI：
10.1196/annals.1308.027
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发表时间：
2004-01-01
期刊：
影响因子：
--
通讯作者：
Higley, JD
中科院分区：
文献类型：
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作者：
Barr, CS;Schwandt, ML;Higley, JD
I型和II型酒精中毒的特征被认为与中枢神经系统5-羟色胺功能失调有关。在这篇综述中，我们在一个非人类灵长类动物模型中讨论了与青少年高酒精消费和其他冒险行为相关的变量。脑脊液中5-羟色胺代谢物5-HIAA浓度较低的青少年灵长类动物更容易冲动，并表现出更高的酒精消耗量。遗传和环境因素都会导致青少年猕猴的饮酒行为。5-羟色胺系统基因中的序列变异，例如单胺氧化酶基因转录控制区的重复多态(MAOA-LPR)，增加了青少年男性饮酒的倾向。环境因素，如同辈养育的早期生活压力或早年接触酒精，也与酒精消费增加有关。同伴抚养的女性，特别是那些在青春期早期接触酒精的女性，与发育后期接触酒精的女性相比，饮酒率更高。当考虑遗传变量时，低活性5-羟色胺转运体基因启动子等位基因(RH5-HTTLPR)与教养条件之间存在交互作用，在雌性个体中存在酒精偏好，而在雄性个体中不存在，这表明基因与环境之间的交互作用可能是性二分的。通过更多地了解青春期非人灵长类动物的基因、早期经验和酒精摄入量之间的相互作用，我们可能能够识别导致冲动控制障碍的易感性、发病机制和进展的因素，如酒精中毒。
Traits characteristic of type I and type II alcoholism are thought to relate to dysregulated central nervous system serotonin functioning. In this review, we discuss variables associated with high adolescent alcohol consumption and other risk-taking behaviors in a nonhuman primate model. Adolescent primates with low CSF concentrations of the serotonin metabolite 5-HIAA are more impulsive and exhibit increased levels of alcohol consumption. Both genetic and environmental factors contribute to alcohol-seeking behavior in adolescent macaques. Sequence variation within serotonin system genes, for example, a repeat polymorphism in the transcriptional control region of the monoamine oxidase gene (MAOA-LPR), increases the propensity for adolescent males to consume alcohol. Environmental factors, such as early life stress in the form of peer-rearing or early age of exposure to alcohol, are also associated with increased alcohol consumption. Peer-reared females, especially those exposed to alcohol during early adolescence, exhibit increased rates of alcohol consumption compared to those exposed to alcohol later in development. When genetic variables are also considered, there is an interaction between the low activity serotonin transporter gene promoters allele (rh5-HTTLPR) and rearing condition on alcohol preference in females but not males, suggesting that the interactions between genes and the environment may be sexually dichotomous. By learning more about the interactions between genes, early experience, and alcohol intake in the adolescent nonhuman primate, we may be able to identify factors that contribute to the susceptibility, pathogenesis, and progression of impulse control disorders, such as alcoholism.